Genomics and Medical Devices

by Food and Drug Administration (FDA)

Imagine that a swipe of the inside cheek or a stick of the little finger could be used to predict whether or not certain types of cancer may be in your future. Theoretically, both can. Thanks to the advances in genetics, and with the clearance by the Food and Drug Administration of a growing list of genetic diagnostic testing devices, doctors are beginning to understand how certain diseases, or increased risks for certain diseases, pass from generation to generation.

The Tag-It Cystic Fibrosis Kit is one such device. Cleared for marketing in May 2005, Tag-It finds genetic variations in what scientists now know is the gene that causes cystic fibrosis — the most common fatal genetic disease in the United States. Made by Tm Bioscience Corp. of Toronto, Tag-It will help diagnose cystic fibrosis in children and identify adults who are carriers of the gene.

Now that the mapping of the human genome is complete, scientists have a resource of detailed information about the structure, organization, and function of the entire set of human genes — all 30,000 to 40,000 of them — and an idea which ones affect health and disease. This genetic reference, coupled with a relatively new research tool called a microarray, provides a snapshot of which genes are active, or expressed, in both healthy and diseased cells. Microarrays allow scientists to view thousands of genes at once. In the past, researchers could study only one or a few genes at a time.

The concept of looking at hundreds or thousands of human genes at one time encompasses the field of science called genomics, and other scientific fields with the shared suffix, "-omics." Some examples include pharmacogenomics: why some drugs work better in some patients than in others; metabolomics: the study of body fluids to determine changes in metabolism; and proteomics: the study of proteins in an organism or tissues.

Building on previous knowledge of the life sciences, the idea is to use these new sciences to develop other ways to diagnose, treat, cure, and even prevent the thousands of diseases that afflict humans. New findings could allow doctors to understand many diseases in much more detail and could help manufacturers design better, faster, and more accurate tests with the ability to predict future health risks. This could mean that doctors will have access to tests that detect diseases before clinical symptoms appear. The -omics technologies currently are also being used by researchers and drug companies to help identify new drug candidates.

Experts at the Oak Ridge National Laboratory (ORNL) — a science and technology lab managed by a main contributor of the Human Genome Project, the U.S. Department of Energy — predict that it won't be long before doctors are able to select specific drugs and specific doses of drugs for an individual based on a decoded copy of his or her own genome. Conceivably, individual genomes could become an essential part of everyone's medical file.

But the road from identifying genes to developing effective drugs and diagnostic devices continues to be both tedious and challenging. Researchers hope that more discoveries made with microarrays in the laboratory will translate into improved genetic and genomic diagnostic tests that will eventually generate the promise of "personalized" medicine, or individually targeted treatments.

The Power of Microarrays

A microarray, or gene chip, is a tiny glass or plastic platform containing thousands of genes. It is similar to a computer microchip, but instead of tiny circuits, the chip contains "probes" or genes with a known identity, such as DNA or small pieces of DNA, which are arranged in a grid pattern on the chip. Whenever genetic material from a patient's blood or other tissue is placed on the chip, the probes react. Those reactions can be detected and used to screen for the presence of particular genetic sequences, such as those related to diseases, and how people will respond to certain medications. Microarrays also can enable researchers to see which genes are being switched on and off under different medical conditions.

"A small amount of body fluid has the ability to look at 35,000 genes that microarrays create," says Raj K. Puri, M.D., Ph.D., director of the Division of Cellular and Gene Therapies at the FDA's Center for Biologics Evaluation and Research. Microarrays can rapidly provide a detailed view of the simultaneous expression of all the genes in an entire genome, and provide new insights into gene function, disease pathology, disease classification, and drug development. "This is a new paradigm of understanding the biology of cells," Puri says.

Microarrays are especially useful because of their small size and because they can contain a very large number of genes. They come in many varieties, either individually created by scientists or produced commercially by a company. But they all share the same principle: a miniaturized slide that carries numerous probes that can measure the expression of genes. They differ in the way the probes are created, as well as in their content. Some of the main challenges in microarray technology result from the technical complexity of the process and the large amounts of data generated by the experiments.

With the development of DNA microarrays, scientists can now examine how active thousands of genes are at any given time. Studying which genes are active and which are inactive in different cell types helps scientists to understand both how these cells function normally and how they are affected when various genes do not perform properly. By comparing genes, scientists can link variations and mutations to many diseases.

Scientists at the FDA's Center for Devices and Radiological Health (CDRH) say that DNA microarrays hold a promise to become useful in earlier diagnosis of diseases such as lung cancer, which usually are not diagnosed until they are well-advanced and less treatable. In the future, microarray-generated data may help doctors with earlier lung cancer classification and diagnosis. But performance of a microarray-based method to test for cancer, the CDRH experts say, has to be properly evaluated before going into the clinic.

Complex techniques such as microarrays leave many opportunities for errors. The lack of standardization for naming and identifying the genes used on different DNA microarray platforms could cause potential errors. Before microarrays can be consistently and reliably used in clinical practice and in regulatory decision making as a diagnostic tool, Puri says that standards, quality measures, format, and interpretation issues still need to be settled.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.